Studies On Secondary Metabolites From Five Streptomyces Strains And Their Biological Activities

Actinomyces is a kind of gram-positive bacteria with high G+C.According to incomplete statistics,there are about 34,000 bioactive compounds found in microbial sources,of which 35 percent are from actinomyces.Streptomyces in actinomycetes is a hotspot in the study of natural products due to continuous discovery of valuable drugs.This dissertation is composed of six chapters.In chapter 1,we describe the isolation,structure identification,and bioactivities of compounds from an endophytic strain Streptomyces sp.KIB-H2054 isolated from plant Campylotropis polyantha.The biosynthetic pathway of three new compounds were also proposed.In chapters 2-5,the detailed chemical studies upon secondary metabolites of four different endophytic strains S.sp.KIB-H1428(from Barleria cristata L.),S.sp.KIB-H1992(from Cassia tora Linn.),S.sp.KIB-H2051(from Magnolia liliiflora Desr),and S.sp.KIB-H1424(from Woodfordia fruticosa(L.)Kurz.)were investigated.The research progress of angucycline group of natural products was reviewed in chapter 6.We initially screened the extract libiary generated from different strains by the chemical profile(HPLC and TLC analysis)and biological activities to select the hit strains.The hit strains were then fermented in large scale to get crude extracts which were further purified by a bunch of chromatographic methods including silica gel column,Sephadex LH-20,MCI,and semi-preparative HPLC to isolate the pure natural products.Their structures of all the 78 compounds isolated from the above mentioned seven endophytic strains were identified and characterized through extensive NMR,UV spectra,IR spectra and MS experiments.Among them,there are 11 new compounds which belong to the congeners of naphthomycins,angucyclines,phenazines and adiposatatin.Six new analogues(1-6)of naphthomycin were isolated from strain Streptomyces sp.KIB-H2054,of which represents three new carbon skeletons and showed better cytotoxic activities against five cancer cell lines than naphthomycin E(9).The biosynthetic pathways of the three new carbon skeletons originated from the common precursor naphthomycin E were also proposed.